The principal aims are to gain a broader understanding of the pathophysiology of immune hemolysis, particularly autoimmune hemolysis, and to determine the relationship of these phenomena to coexisting malignant disease. The work will be concerned with: 1) The preparation, characterization and clinical evaluation of anti-complement antiglobulin reagents of different specificities (e.g. anti-C3c, C3d, C4c, C4d, C5, C6). Emphasis will be placed on defining the specificities most appropriate for diagnostic vs cross-matching use, with provisional guidelines for standardization of such reagents. 2) Serum concentrations and equilibrium constants (Ko) will be determined for anti-C3d antibodies in whole sera from hyperimmunized animals and in commercially prepared anti-C3d reagents. The stability of these antibodies during storage at -80 degrees and 4 degrees centigrade will be defined. Antibody concentrations and Kos will be correlated with anti-C3d agglutination titers. 3) Well-characterized anti-C3d antibodies will be labelled and empolyed to quantitate RBC-bound C3d: a) from normal subjects, freshly obtained and following storage at 4 degrees centigrade with and without anticoagulant preservative solutions, b) from patients whose illness does not primarily involve the immune system, c) from patients with primary immune system disease (especially lymphoreticular malignancies and dysproteinemias), d) from patients with other malignancies to which an immune response is suspected, and e) normal RBC to which complement has been bound in vitro by immune-mediated or chemical means, to determine the reproducibility of the in vitro binding systems and the stability of the bound C3d during subsequent 4 degrees centigrade storage of the coated RBC. 4) Studies of the incidence of autoantibodies of multiple immunoglobulin classes (IgG, IgA, IgM) in eluates from red blood cells sensitized in sera containing high titer cold agglutinins, and in sera and eluates from red cells of patients with warm AHA. 5) Participation in a collaborative study of the incidence of HLA sensitization in patients who have received transfusions only of a) previously frozen, thawed processed donor red blood cells, or b) donor red cells depleted of leukocytes and platelets by sedimentation in hydroxyethyl starch.